The overall research aim of this Center of Excellence in Malaria Research is to organize a comprehensive approach to understanding the biological features of Amazonian malaria towards the ultimate goal of regional control and elimination of Plasmodium falciparum and P. vivax. We focus primarily on P. vivax due to its greater impact in the region. We anticipate that the lessons learned will contribute towards the audacious goal of global malaria eradication. An integrated and interactive set of 5 projects will be supported by Administrative, Data Management and Shared Laboratory Resource Cores to study malaria epidemiology, vector biology and ecology, diagnostics, transmission biology and clinical pathogenesis towards the goal of malaria control, regional elimination and eradication in the Amazon region of South America. Three epidemiological distinct sites primarily affected by P. vivax (~80% of cases) but also by P. falciparum (~20%) of cases will be studied: Acre, Brazil;Iquitos, Peru;and Madre de Dio/Puerto Maldonado, Peru. Investigators from University of Sao Paulo and the Universidad Peruana Cayetano Heredia in Lima, Peru will be the lead foreign collaborators, and will join forces with lead institution University of California San Diego, and collaborating institutions Wadsworth Center of the New York Health Department, Johns Hopkins School of Public Health, and the U.S. Naval Medical Research Center Detachment, Lima, Peru to carry out the aims of the Center. RELEVANCE: The Peru/Brazil Center of Excellence in Malaria Research will take an integrated approach to the study of malaria epidemiology, vector biology and ecology, diagnostics, transmission biology and clinical pathogenesis to underpin malaria control, elimination and eradication efforts in the Amazon region of South America. PROJECT 1: Title: Epidemiology of Malaria in the Peruvian and Brazilian Amazon Project Leader: Ferreira, M. PROJECT 1 DESCRIPTION (provided by applicant): Institutions based in two malaria-endemic countries, Brazil and Peru, are partnering with a leading research group in the USA with the long-term goal of providing scientific evidence that can be translated into effective public health interventions for malaria control in Amazonia. To determine whether asymptomatic parasite carriage is a major contributor to malaria transmission across the region, we aim: (a) to estimate the prevalence, incidence and risk factors for asymptomatic malaria parasite carriage in rural Amazonia;(b) to estimate the prevalence, incidence, average duration and risk factors for gametocyte carriage;(c) to compare the ability of symptomatic and asymptomatic carriers of gametocytes to experimentally infect wild-caught local vectors;(d) to compare prospectively the risk of subsequent clinical malaria among asymptomatic parasite carriers and non-infected controls living in the same communities and to determine whether these episodes are due to persistent parasite lineages or to new infections;and (e) to test whether intra-host competition of genetically distinct parasite clones contributes to increased parasite virulence, greater risk of disease, and increased gametocyte production. These aims will be achieved with population-based surveys, using uniformized clinical and laboratory protocols, in three epidemiologically diverse Amazonian settings: (a) a typical agricultural settlement with endemic malaria transmission in Brazil, (b) periurban villages in Peru that became recently exposed to epidemic malaria, and (c) gold-mining enclaves in Peru with explosive malaria outbreaks due to P. vivax. The field-based clinical and epidemiological analysis will be complemented with measurements of immunological parameters, extensive parasite genotyping and experimental infections of mosquitoes through membrane-feeding assays, providing a unique multidisciplinary perspective on the public health significance of asymptomatic parasite carriage in the Amazon Basin. Of crucial importance, the infrastructure and the data resulting from seven years of active malaria surveillance in the field sites will establish the bases for the vector biology and pathogenesis components of this proposal and for implementing future malaria vaccine trials in the Amazon region. RELEVANCE: At a time when eradication is advocated as the ultimate goal of malaria control strategies worldwide, it remains unclear why malaria proved so difficult to control in areas of relatively low levels of transmission across the Amazon Basin. We hypothesize that asymptomatic infections may represent a major reservoir of parasites in this region, which is not addressed by traditional malaria control strategies.